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Simulated Microgravity Increases ß-Adrenergic Lipolysis in Human Adipose Tissue¹

Institut National de la Santé et de la Recherche Médicale U-317, Laboratoire de Pharmacologie Médicale et Clinique, Centre d’Investigation Clinique, and Laboratoire des Adaptations de l’Organisme à l’Exercice Musculaire, Université Paul Sabatier, 31073 Toulouse, France

Address all correspondence and requests for reprints to: Dr. Michel Berlan, INSERM U-317, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 Allées Jules Guesde, 31073 Toulouse Cedex, France. E-mail: berlan{at}cict.fr

The effect of a sustained decrease in sympathetic nervous activity, achieved through 5-day head-down bed rest (HDBR), on the ß-adrenergic lipolytic activity of sc adipose tissue was studied in eight healthy men. The in situ ß-adrenoceptor (AR) sensitivity was studied using the microdialysis method. Local perfusion of increasing concentrations of isoprenaline showed an increased ß-AR sensitivity to lipolysis (assessed by extracellular glycerol concentration) and to vascular tone (assessed by the ethanol clearance). The adrenergic sensitivity of isolated adipocytes was studied in vitro. Basal lipolysis and the response to nonselective (isoprenaline) or selective (dobutamine, terbutaline, and CGP 12177) ß-AR agonists were increased after HDBR as was the lipolytic effect of dibutyryl cAMP. When data were expressed as a percentage of the dibutyryl cAMP effect to rule out the postreceptor events, basal and lipolytic responses to ß-AR agonists where similar before and during HDBR. The ₂-AR-mediated antilipolytic effects of adrenaline were not modified. Lymphocyte ß-AR number was unchanged during HDBR. Our results demonstrate that a sustained sympathoinhibition induces an increase in the lipolytic ß-adrenergic response in adipose tissue and suggest that this hypersensitization is linked to an increase in the postreceptor steps of the lipolytic cascade in the adipocyte rather than to changes in ß-adrenoceptors.

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